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Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: role of serotonin synthesis.

Abstract：

:We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function, and attempted to identify underlying mechanisms. Biochemistry of serotonin was assessed with brain tissue assays and microdialysis; behavior was assessed as the acoustic startle reflex. Long-term SSRI administration to rats reduced the content of 5-HT and its main metabolite shortly after inhibition of 5-HT synthesis in many brain areas with more than 50%. Turnover was not appreciably decreased, but significantly increased within 48h of drug discontinuation. The microdialysis experiments indicate that neuronal release of 5-HT depends strongly on new synthesis and emphasize the role of 5-HT(1B) receptors in the regulation of these processes. Discontinuation of the SSRI rapidly increased behavioral reactivity to the external stimulus. Additional startle experiments suggest that the increased reactivity is more likely related to the reduced extracellular 5-HT levels than to impaired synthesis. The combination of the marked reduction of serotonin content and limited synthesis may destabilize brain serotonin transmission during long-term SSRI treatment. These combined effects may compromise the efficacy of an SSRI therapy and facilitate behavioral changes following non-compliance.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Bosker FJ,Tanke MA,Jongsma ME,Cremers TI,Jagtman E,Pietersen CY,van der Hart MG,Gladkevich AV,Kema IP,Westerink BH,Korf J,den Boer JA

doi

10.1016/j.neuint.2010.10.001

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

948-57

issue

8

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(10)00305-0

journal_volume

57

pub_type

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